The geo-referencing accuracy of the images acquired by a UAV based multi-sensor system is affected by the accuracy of the mounting parameters involving the relationship between a camera and a GPS/INS system as well as the performance of a GPS/INS system. Therefore, the estimation of the accurate mounting parameters of a multi-sensor system is important. Currently, we are developing a low altitude multi-sensor system based on a UAV, which can monitor target areas in real time for rapid responses for emergency situations such as natural disasters and accidents. In this study, we suggest a system calibration method for the estimation of the mounting parameters of a multi-sensor system like our system. We also generate simulation data with the sensor specifications of our system, and derive an effective flight configuration and the number of ground control points for accurate and efficient system calibration by applying the proposed method to the simulated data. The experimental results indicate that the proposed method can estimate accurate mounting parameters using over five ground control points and flight configuration composed of six strips. In the near future, we plan to estimate mounting parameters of our system using the proposed method and evaluate the geo-referencing accuracy of the acquired sensory data.